Aerosol therapy is a very important administration route in the treatment of lungdiseases such as asthma, chronic obstructive pulmonary disease (COPD), cysticfibrosis (CF) and bronchopulmonary dysplasia (BPD). Aerosols are also used todeliver systemic drugs such as vaccines, insulin, antibiotics and pain medications. Totreat these diseases effectively with medical aerosols one needs to understand thebasics of aerosol science and the operating principles of the devices available.

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Inhaling medication is difficult for a significant amount of patients. This has beendemonstrated in many of studies. Device instructions for use that come with thedrug, does not lead to a perfect inhalation technique, not even immediately afterreading the instructions and practicing with the device. Inappropriate devicetechnique is due to the lack of formal patient training.

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The purpose of this course is to increase your knowledge of the basic science ofaerosol drug delivery. The course will cover the rationale, influencing factors andapplication of inhaled drug therapy. The focus will be on the concept of particle sizeas it relates to deposition in the respiratory tract and the detail of the three deviceplatforms including pMDI, DPI & jet nebulizers.

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Methods for generating aerosols, formulating drugs, and administering medicationseffectively to the desired site of action constitute the science of respiratory drugdelivery.

Nebulization of substances for inhalation is among the oldest methods of deliveryto the lung. The earliest reports can be traced back to the middle of the 19thcentury; European spas used systems to deliver thermal aerosolized water to treatlung afflictions. Smokers and drug abusers discovered that by inhaling substancesinto their lungs, the desired effect would be quicker, they would not need as muchof the substances, and other elements of delivery could be eliminated, such asneedles. 1

The inhaled route has several advantages as demonstrated by the therapeuticwindow graph. Drug delivery via the lung allows direct delivery to the site of action,for small quantity of drug to be enough for an adequate response, an onset ofaction that is usually faster, and the systemic bioavailability has less variability inside effects and efficacy than other drug delivery methods. 2

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Successful drug delivery to the lung is dependent on a variety of factors such as thephysical characteristics of the aerosol, the device that is used to deliver the drug,the patient, the drug and the disease. 3

Understanding the physical nature of aerosolized particles deposited within thehuman respiratory tract is a key part to understanding how respiratory drug deliverydevices operate, Aerosols exist everywhere there is gas to breathe. From pollensand spores, to smoke, pollution and man‐made chemicals, aerosols include any fineliquid or solid particles. Every day billions of particles are inhaled with ambient airby every human being. Our airways are constantly filtering and removing unwantedparticles.4

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Aerosol therapy provides a fast, effective route for treating lung disorders because the drug is delivered to the site of action. Aerosol therapy is most commonly used to prevent or treat bronchospasm, prevent or treat inflammation, liquefy and mobilize secretions, and prevent or treat respiratory infections. 

Aerosol therapy is also used to deliver systemic drugs such as vaccines, insulin and pain medications. 5 and 6 

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The primary reasons for utilizing respiratory drug delivery are; speed of action, lessside potential effects and its comfort.

Respiratory drug delivery is in the management of chronic and acute respiratorydisease. However, respiratory drug delivery is also used for systemic drug delivery.Examples include vaccines, pain medications, antibiotics and insulin.

The factors that influence drug delivery to the lung will be discussed in the nextsection.

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The purpose of a respiratory drug delivery device is to create aerosolized particlesan or facilitate aerosol delivery to the lungs. The mechanisms of particle delivery tothe lungs will be discussed in this section.

Understanding the physical properties of aerosolized particles is key to understanding howrespiratory drug delivery devices operate.

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Our respiratory system’s evolved filtration and elimination mechanism is animpediment to respiratory drug delivery. The nose removes particulate matter webreathe from the air before it deposits in the airways. Nasal hairs filter out largeparticles (greater than 15μm in diameter). The respiratory tract has a variety ofstrategies for dealing with particles that bypass the nose. Coughing and sneezingreflexes triggered by airway irritation, accelerate the movement of particles up theconducting airways and out of the body. 7 and 8

Medicinal particles however, are sized and shaped to overcome our respiratoryfiltration system. Their deposition in the respiratory tract may be predicted.

Patients inhale drug particles for the treatment of respiratory diseases generated byformulations especially designed for this purpose. In contrast to ambient particles,medicinal particles are distributed over a limited size range: their shape andcomposition are known, and their deposition in the respiratory tract may bepredicted rather precisely. 9 and 10

Respiratory drug delivery devices do not produce particles of just one size. Theyproduce particles in a variety of sizes. The size of the particle produced by thedevice determines how deep the particle can penetrate into the respiratory tract.Smaller particles penetrate deeper into the lung and may allow the inhaledmedication to work more effectively. 11 and 12

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Particle size is measured in microns.1 micron is 1 millionth of a meter (1 thousandthof a millimeter). To understand how small that is, a human hair is between 40‐60microns. The eye cannot see discrete particles below 25‐30 microns. Particles thatare between 1‐5 microns are considered to be respirable. 13

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The factors affecting particle delivery to the lung are: Size ‐ The physical property of theaerosol itself is the aerodynamic diameter. The ideal size for therapeutic aerosols is < 5microns to penetrate the tracheobronchial tree. In order to evaluate and compare theefficiency of devices, the particle size must be measured and statistically described.

A descriptive term that is often used in the evaluation of particle size is Mass MedianAerodynamic Diameter (MMAD). MMAD is a multi‐dimensional measurement used toevaluate particle size and its relationship to the mass (volume) of the aerosol produced. Itis used to determine the depth of potential penetration of an aerosol particle into therespiratory tract.

The graph shows the diameter at which half of the aerosol particles are larger than theMMAD and half of the aerosol particles are smaller than the MMAD. In this graph, theMMAD is 10μm. MMAD is measured by cascade impaction. Cascade impaction is an invitrotest that measures the size of particles based on their behavior in an air‐stream. The massof drug particles with a given aerodynamic diameter is analyzed.

Physical properties of the particle play an important role in the potential for delivery ofparticles to the lung. The shape, gravity and motion also impact the penetration ofparticles.

Aerosol testing is usually performed under simulated use conditions in a lab and it isassumed that patients will follow the instructions for use to optimize drug delivery.However, for many patients, aerosol devices are difficult to use without properhands‐on training. The age and disease state of the patient play major role in drugdelivery to lungs. For example, a COPD patient’s airway is obstructed and resistantto air flow. That may lead to large airway particle deposition. Therefore, breathingtechniques are needed to maximize drug delivery to their lungs. 16 and17

To understand the role the device plays in drug delivery, it is important to know howit operates and the factors that will optimize utilization such as; clinical setting,patient age and the ability to use the selected device correctly, device use withmultiple medications, cost and reimbursement, drug administration time andconvenience. 18

The next section will explain the operation of commonly used drug delivery devices.

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As mentioned previously, successful drug delivery to the lung is dependent on avariety of factors such as the physical characteristics of the aerosol, the device usedhave the potential to deliver the drug, the patient, the drug and the disease. Thefirst portion of the course focused on understanding the physical nature ofaerosolized particles and where they are deposited within the human respiratorytract. This portion of the lecture will focus on understanding how aerosol deliverydevices operate.

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Despite the numerous methods that can be employed to generate aerosols intherapeutically useful particle size ranges and concentrations, only three basicaerosol delivery systems have found their way into commercially marketed drugproducts: metered dose inhalers (MDIs), Dry Powder inhalers (DPIs) and jetnebulizers.

None of these devices can be precisely dosed in a single breath, but aremanufactured to achieve minimally acceptable dose. To be acceptable for clinicaluse the inhalation system must meet certain criteria: simple, convenient,inexpensive and portable.

Device and drug formulations undergo extensive clinical trials and regulatoryapproval before being released. However, there is no perfect, fail‐safe, error‐proofrespiratory drug delivery device on the market today. For many patients, drugdelivery devices are difficult to use without proper training. 19

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Since the 1950’s MDIs have been a mainstay of the respiratory drug delivery devicesbecause they are compact, portable, provide multi‐dosing and are perceived to be easy touse. Each MDI has a specific formulation and dose of drug depending upon the specificdrug. Formulations include the drug as well as propellant and other things called excipientsthat help aerosolized the contents of the MDI. Each actuation of the inhaler is associatedwith a single inspiration of the patient. The MDI is typically a single patient use device thatis dispensed from the pharmacy with a specific quantity of medication and disposed ofwhen the medication has been depleted. 20, 21 and 22

The next few slides will examine the components and operation of the MDI; discussadvantages and disadvantages of the MDI.

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Since its development by Dr George Maison in 1955, the pressurized metered‐dose inhaler(pMDI) has been the most common aerosol generator prescribed for patients with asthmaand COPD. This is because it is compact, portable, easy to use, and provides multi‐doseconvenience. 23, 24 and 25

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Regardless of the manufacturer or active ingredient, the basic components of the pMDIinclude; an actuator nozzle, expansion chamber, metering valve, canister, gas phase orpropellant vapor, formulation (liquid drug propellant mixture), metering chamber andactuator.

The metering valve is crimped onto the mouth of the canister, and the entire system isenclosed in the actuator through which inhaled ambient air is drawn in by the patient.

A typical canister may contain 150‐300 doses of medication. A pre‐measured amount ofdrug is delivered per actuation when the device is shaken inverted and the canisterdepressed. 26, 27 and 28

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When the device is actuated, the canister is exposed to atmospheric pressure, which leadsto aerosolization (high velocity spray) of the drug. As it travels through the air, the aerosolwarms, leading to evaporation of the propellant but the drug remains unchanged.Evaporation reduces the particle size to the desired range.

As the particles travel, they slow down as they collide with the surrounding air. The particlesize emitted from the MDI is dependent on the vapor pressure of the propellant anddiameter of the actuator opening. The size of particles emitted from these devices will bereduced as vapor pressure is increased and diameter of the actuator decreases. 29 and 30

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A common end user problem that can prevent the metered amount of drug from reachingits target is not following the required steps for using a MDI.

Not shaking a pMDI canister that has been standing for a short time can decrease therespirable dose as much as 25% and 35%. This is because the drug in the canister is usuallyseparated from the propellants when left standing. Therefore, MDIs must be shaken beforethe first actuation after standing in order to refill the metering valve with adequately mixedsuspension from the canister.

Priming the MDI is also required after being unused for a period of time. Priming isreleasing one or more sprays into the air. It is required because the drug may be separatedfrom the propellant in the metering valve when the pMDI is new or has not been used for awhile. Because shaking the pMDI will mix the suspension in the canister but not themetering chamber, priming of the pMDI is required.

Storage Temperature: Outdoor use of pMDIs in very cold weather may significantlydecrease aerosol drug delivery. For example, dose delivery from HFA‐MDIs decreased by70% over the range of ‐20 to 20 ºC (44)

Cleaning: The amount of medication delivered to the patient is dependent upon themetering valve, cleanliness and the lack of moisture. The actuator nozzle is pMDI specificand the coordination of the nozzle with the medication will influence both inhaled doseand particle size. White and crusty residue due to lack of cleaning may crystallize the

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medication and influence drug delivery. Therefore, the nozzle should be cleaned periodicallybased on the manufacturer’s recommendations 30, 31, 32 and 33

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Only a small fraction of the drug may reach the lung if there is poor coordination betweenactuation and inhalation. 34

Some common hand/breath problems include firing into mouth while breathing throughthe nose, firing before start of inhalation and firing after inhalation and multiple actuationsduring a single inhalation.

It is also important to wait 60 seconds between each actuation. With each actuation thereis a cooling of the contents and, if the contents are not allowed to re‐warm, thepredictability of the aerosol produced is poor when the contents are cool.

Inappropriate inhaled flow rate – to minimize impaction the patient must breathe in themedication slowly or less than 60 LPM. A breath hold after actuation is important tomaximize particle deposition through sedimentation and diffusion. The longer a patientholds the drug in their lungs, the better the opportunity for the particle deposition and thefewer particles are exhaled. 35, 36 and 37

This radioscintigraphic picture demonstrates what can happen when a pMDI is not correctlyused. Drug is deposited in the mouth, posterior pharyngeal and stomach region.

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The steps required for MDI use make it difficult for the patient to properly inhale the drug.

It is especially difficult to make a child or infant inhale the prescribed medical substances inthe proper way. Children and infants have limited lung capacity and the force of a child's orinfant's breath during inhalation (inhalation flow) is thus limited. This is even more so whenthe child or infant is suffering from asthma or other bronchial diseases. 38 and 39

For patients of limited or compromised inhalation capacity, inhalation through a MDI maybe accomplished through the use of a spacer or valved holding chamber. 40, 41 and 42

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The picture shows the spray differences between HFA‐pMDIs and CFC‐pMDIs. HFA‐pMDIshave a softer spray than do CFC‐pMDIs. With a HFA propellant, the spray is propelled at aslower rate as shown in the picture. A slower velocity theoretically will improve drugdeposition. However the HFA slower spray does not eliminate problems associated withcoordination. This is especially true for small children who require a valved holdingchamber (VHC). VHCs and spacers will be discussed in the next few slides. 43, 44, and 45

Additionally, actuation with breath moisture may cause an HFA propelled metering valve tostick, therefore the canister should not be immersed in water. The float test that was usedto determine canister load with CFC MDIs, is no longer recommended. Some newer HFAMDIs have dose counters but many do not and patients must keep track of actuations. Theonly method to determine the number of doses remaining in a HFA MDI without a dosecounter is to count actuations manually. Manual methods include reading the label todetermine the total number of doses available in the pMDI, and using a log to indicateevery individual actuation given, including both priming and therapy doses. This tally issubtracted from the number of actuations on the label until all have been used.

Mouthpiece cleaning is recommended on a weekly basis. A moist cotton swab can be usedto clean the circular opening by twisting the swab in circular motion to remove residue.More information is available on the device/drug insert or available on‐line. Primingguidelines vary by product. 46, 47, 48 and 49

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The design advantages of MDIs are listed above. Over the years a number of deficiencieshave been identified and are listed under the disadvantages column. 50, 51 and 52

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Although the presence of a one‐way valve prevents aerosol particles from exiting thechamber until inhalation begins, optimal aerosol dosing still depends on inhaling as close toor simultaneously with pMDI actuation.

Time delays can reduce the available dose for inhalation from a valved holding chamber.The one‐way valve should have a low resistance so that it opens easily with minimalinspiratory effort. Ideally, there should be a signal to provide feedback if inspiratory flow istoo high. 53

The animation shows how the VHC traps large droplets that are emitted from the MDIallowing smaller particles to be inhaled.

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The use of a spacer or valved holding chamber (VHC) can improve the effectiveness ofMDI drug delivery and reduces oropharyngeal deposition by adding volume and spacebetween the metering valve and the patient’s mouth. 54, 55 and 56

A metered dose inhaler (MDI) is a handheld pressurized metal canister that contains apharmacological agent in suspension or solution, a surfactant, a propellant, a meteringvalve, and a mouthpiece for drug delivery. On actuation (i.e., the canister being triggered todeliver a dose), a fine atomized spray occurs over 100‐200 milliseconds to deliver the dose(the delivered dose is dependent on the product used.)

MDI disadvantages include; requires priming, cleaning and correct actuation and inhalationcoordination. Incorrect use results in oropharyngeal drug deposition

Valved Holding Chambers and spacers improve the effectiveness of MDI drug delivery andare recommended for patients who have difficulty with breath actuation/ coordination i.e.small children

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Dry powder inhalers (DPIs) are portable, inspiratory flow‐driven devices that are used toadminister dry powder formulations to the lungs. They have been developed to overcomethe difficulties of using metered‐dose inhalers and are often prescribed with the hope ofproviding the patient with an overall more user‐friendly and more predictable therapy.

Over the past two decades, the market for dry powder inhalers (DPIs) has significantlyincreased. Advair® is a example of a DPI that is used in the management of chronicrespiratory diseases. DPIs are also the device of choice for systemic drug delivery. Systemicdrugs like vaccines and insulin for the treatment of diabetes are available in dry powderformulations.57

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The first DPI introduced to the market was cromolyn containing Spinhaler, in 1971. It wasnot widely accepted due to the amount of powder that the patient needed to inhale intotheir lungs and fear of inhaling capsule fragments.

DPIs were developed to overcome the MDI disadvantages that we discussed earlier, such asdose counters, propellants and breath actuation problems 58

The next slide will detail the operational aspects of the DPI.

The DPI procedure begins with the loading of a factory filled hard gelatin capsule oraluminum laminate blister that contains a mix of powder (carrier) and fine micronized drugparticles into a inhalation chamber. After loading the capsule into the inhalation chamber, itis rotated and pierced. Once pierced, the powder is pulled through the chamber by thepatient’s own inspiratory flow via the DPI mouth piece. The airflow dilutes the powder andpropels it into a mesh or screen where the small particles are sheered from the powderand is converted into an aerosol. The patient is instructed to holds their breath for 5‐10seconds to ensure adequate particle deposition. The dose that can be delivered is typicallyless than a few milligrams in a single breath since larger powder doses may lead toprovocation of cough. 59 and 60

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DPIs can be divided into their dose carrying capacities: Single Dose DPIs, Multiple Unit‐Dose DPIs and Multiple Dose DPIs. Single‐dose DPIs use a single‐dose capsule, multipleunit‐dose DPIs use single doses that are loaded into individual blisters and multiple‐doseDPIs use either a reservoir or blister strips, designed to deliver repeated doses. Regardlessof the type of DPI, they all operate as described in the previous slides.

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Advair Diskus® is the most popular DPI and is a multiple dose DPI system. The doses arefactory loaded and individually sealed in foil packets that protect them from moisture andhumidity. 61 and 62

Resistance & Inspiratory Flow: Each type of DPI has a different intrinsic resistance to airflowthat determines how much inspiratory flow needs to be created in the device to releasethe correct amount of drug. To give an example, the Twisthaler has a higher resistance thandoes the Diskus® and therefore requires a greater inspiratory effort. As demonstrated bythe graph, the Diskus and the Twisthaler have a higher resistance profile than the 3M HFApMDI. 63 and 64

When the patient inhales through the DPI, she or he creates an airflow with a pressuredrop between the intake and exit of the mouthpiece. Thus, the patient can lift the powderfrom the drug reservoir, blister or capsule depending on the model being used. Thepatient’s inspiratory effort is also important in deaggregating the powder into finerparticles. 65

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In addition to overcoming DPI flow resistance, patients often fail to follow the instructionsfor use. In 2004, Dr. Melani published common DPI technique problems. The study showsthat 35% of the patients that were observed did not hold the device correctly. The studyalso revealed that the observed patients did not coordinate the breathing pattern requiredfor optimal drug delivery. 66

This again underlines the point, if a patient is using it incorrectly, he/she will have poorclinical results. When a medication delivery system such as a DPI is used incorrectly, apatient is likely to compensate by taking more puffs than actually needed and the potentialfor unwanted medication side effects. Appropriate education on medication deliverysystems is essential.

The portability, built in dose counter, and breath‐actuated features are advantages that aDPI has over a MDI and jet nebulizer. Additionally, there is no priming requirement, thedose carrying capacity is higher, and the drug is more stable than the propellant drivenMDI. A good example of a popular DPI is the Advair Diskus

However, the patient’s inspiratory flow may not be adequate enough to draw the drug fromthe device and problems can occur when the patient does not follow the instructions foruse. For example, the patient should know how to correctly hold the device while inhalingand not exhale into the device. This will optimize drug delivery and prevent theintroduction of ambient humidity into the mouthpiece resulting in a negative effect to themedication. 67

It is important to make sure that the patient understands how the DPI works and how itshould be used. The following slides will review the resistance of DPI and common patientuse errors.

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DPIs were developed to overcome the difficulties of using metered‐dose inhalers and areoften prescribed with the hope of providing the patient with a more user‐friendly and morepredictable therapy.

DPIs have both advantages and disadvantages as seen in previous slides. Because they donot require hand‐breath coordination, the patient’s inspiratory flow should be adequateenough to draw the drug from the device. It is important that the patient understands howthe DPI works and how it should be used.

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The third and last respiratory drug device nebulizers are commonly used in hospitals and bypatients who are unable to operate and coordinate a pMDI or a DPI. The first few slides willdiscuss the basic operating principles of the pneumatic jet nebulizer and then discussdifferent types that are currently available and their advantages and disadvantages. Breath‐actuated and ultrasonic vibrating mesh nebulizers will also be discussed towards the end ofthis chapter.

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Jet nebulizers use inhaled drug solutions that may not be available in pMDIs or DPIs (e.g.antibiotic drug solutions). In terms of breath coordination and procedure, the jet nebulizeris probably the simplest inhaler type for a patient to use if we assume that assembly,proper cleaning and maintenance is not a problem.

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Operation as follows:

Air is drawn into a compressor and is filtered before it reaches the inside of thecompressor. Compressed air is delivered through a plastic tube which connects to the baseof the nebulizer hand‐set cup that contains the liquid drug. The nebulizer aerosolizes theliquid drug and makes it available through a mouthpiece or an aerosol mask. The aerosol isdelivered to the lungs. 68, 69 and 70

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The liquid drug is drawn from the nebulizer cup into a jet by a combination of gas flow andpressure. Small droplets are aerosolized out while large droplets are re‐circulated. TheBernoulli’s principle is the reason the liquid is drawn up into the jet. Bernoulli was a Swissmathematician born in 1740 who studied the flow of liquids and came up with his principlewhile looking at the river. The principle states that when a flow enters a constriction,velocity is increased and lateral pressure is reduced. 71

The next step is refining the liquid to sheer it into small particles (cavitations). This isaccomplished by impaction against baffle. The baffle is simply a piece of material placed inthe stream of particles onto which they impact and break up into smaller particles. Smallerparticles are able to flow into the mouthpiece and avoid impact. The large droplets are re‐circulated. 72

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Studies have shown that as the gas flow rate increases, the particle size produced by thenebulizer decreases. The graph shows particle size reduction of four different nebulizers atthree different (4, 6 and 8 lpm) flow rates. Higher gas flow rate will decrease the amount oftreatment time needed to deliver the set amount of drug. 74 and 75

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A minimum amount of gas flow ranging from 2 – 8 lpm is needed to convert the liquidmedication into an aerosol. In the hospital, compressed (piped‐in 50 psig) air or oxygen isoften used to power a pneumatic jet nebulizer.

Compressors are usually the only option available for jet nebulizer home use. Compressorsare electronically powered, durable and portable. Room air is drawn in and compressedthen immediately forced out again. Portable compressors offer a DC power source and canoperate at lower flow rates.

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Various types of pneumatic jet nebulizers are available on the market today. There are fourdifferent designs of the pneumatic jet nebulizer: Conventional jet with reservoir tube, flow‐enhanced passive venturi, breath‐enhanced active venturi and breath‐activated or actuatednebulizer. The next few slides will detail the design and the advantages and disadvantagesof each one 76, 77, 78 and 79.

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The components of the conventional jet nebulizer consist of a medication cup, amouthpiece attached to a T‐shaped piece, a plastic tube that connects the gas source tothe nebulizer cup and a six inch length of corrugated tubing. The respirable particlesproduced by the conventional jet nebulizer are between 10‐20%. The medication availablefor inhalation is restricted, because the patient’s inspiratory flow is much greater than thenebulizer’s output of aerosol.

In order to decrease drug loss and increase inhaled mass, a t‐piece and large bore tubingare attached to the expiratory side of the nebulizer.

Additionally because standard jet nebulizers are inexpensive to produce, there is a widevariation in aerosol characteristics from unit to unit, batch to batch. The plastic aconventional jet neb is made from is not durable. Because both air and liquid is forcedthrough the jet at a high velocity this, combined with the relatively cheap plastic that thenebulizer is made from, results in erosion of the jet. This reduces the therapeutic benefit ofthe aerosol. The output is highly variable. 80 and 81

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The plastic used to make these conventional jet nebulizers is not durable and does notwithstand the air and liquid that is repeatedly forced through at a high velocity. Over time,the quality of the jet stream is eroded and therapeutic benefit of the aerosol is reduced.The output is highly variable and will not be able withstand repeated cleanings. 82, 83, 84, 85, 86,87 and 88

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A passive venturi (also known as flow enhanced) nebulizer utilizes an open‐vent design.This design has been evaluated in several studies, which have reported greater pulmonarydeposition with this design than with a conventional nebulizer. The advantage of theventuri design is an improvement in nebulizer output with an increase in flow. This is aresult of the air flow coming into the nebulizer cup from the top of the nebulizer via theventuri. The venturi airflow is combined to the flow coming from the source gas increasingthe probability of matching the patient’s peak inspiratory flow with aerosolized medication.The SideStream is a flow enhanced nebulizer. 89, 90 and 91

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The total chamber flow will vary with the patient’s inspiratory effort. 92, 93 and 94

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When the patient inhales, the flow from the gas source combines with additional flow froma venturi and increases total flow going through the nebulizer cup. The patient’s inspiratoryflow rate pulls the venturi valve open and therefore, total chamber flow will vary with thepatient’s inspiratory effort. When the patient exhales the venturi valve closes and theexhalation valve opens.

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The breath‐actuated jet nebulizer or as it is sometimes referred to the dosametric nebulizeris relatively new to the jet nebulizer market. It is primarily used in the hospital and as itsname implies, it is activated by the patient’s breath or on inspiration.

While this nebulizer is unique in the way it is activated, it is like all other jet nebulizers interms of a gas flowing through a supply tube to the jet. Nebulizer jets we have previouslydiscussed need a minimal gas flow of six liters of gas flow to draw fluid in to the jet fornebulization. This nebulizer requires eight liters of flow to power its jet, making thisnebulizer difficult to use without a high gas flow source.

Similar to the inspiratory valve action of the breath enhanced jet nebulizer, the breathactuated jet nebulizer has an active venturi that opens on inspiration and closes onexhalation, allowing the nebulizer to match the patient’s peak inspiratory flow. Onexhalation, the breath actuated nebulizer uses a spring‐valve to stop air flow to jet nozzleduring exhalation.

The feature of a breath‐actuated nebulizer serve to preserve medication for inspiration,however, because it is active on inspiration only, a standard dose of liquid medication couldtake twice as long to nebulize as a standard jet nebulizer. As a means to shorten treatmenttimes, hospital based clinicians will use an undiluted liquid medication, reducing thevolume of liquid in the nebulizer cup. This practice must be monitored closely for any signsof side effects that may result from using high dose medications. High cost compressor

flow requirements and longer treatment times, cause the breath activated nebulizer to beseldom used in the home. There are some limitations in the hospital as well, he nebulizerdoes not fit standard masks and can’t be used in‐line with a ventilator. 95, 96, 97, 98, 99, 100, 101 and102

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Hospitals have used ultrasonic nebulizers since the 1970’s. These were generally used toinduce sputum. High frequency sound waves are applied to a piezoelectric transducer tocreate vibrations. The vibrations pass through the solution that breaks the surface of theliquid into small particles. The ceramic piezo element bonds to a metal shim and thisvibrates in response to alternating voltage (+/‐ 12V, 2 MHz). The higher the frequency thehigher the aerosol output and more heat is generated. Droplets are produced by surfacevibration and cavitation and as is the case with compressor driven jet nebulizers, largedroplets are re‐circulated. 103, 104 and 105

The newer generation of ultrasonic nebulizers is more portable, efficient and quiet than thepneumatic jet nebulizer compressor systems. The mesh technology used in these devicesensures precise and consistent drug delivery to the lung.

Aerosol is generated by vibrating plate apertures or a horn that employ a mesh to generateprecise particle sizes. 107,108 and 109

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110, 111 and 112

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In conclusion, the ideal device must produce the highest possible respirable mass. It mustwork properly across a wide range of inspiratory flow rates to ensure optimal delivery andefficacy. To eliminate errors in use the device should be easy to use and to prevent loss ofmedication it should To improve compliance with use of these devices, it must be highlyportable.

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